We are proud to present the SERCEB (Southeast Regional Center of Excellence for Emerging Infections and Biodefense) plan for the next five years of research, training and emergency response. Our organizing theme is "host-pathogen interactions: opportunities for intervention." We bring together an integrated and experienced team of superb investigators in virology, bacteriology, immunology, drug discovery and vaccine development whose ability to work together has been clearly demonstrated in the past five years. We believe our group is second to none, and look forward to the challenges and opportunities ahead with great confidence in our ability to deliver the highest quality discovery science, and in our ability to deliver clinically useful products. We work together in synergistic teams that span boundaries between universities, between basic scientists and public health workers,.and between academia and private enterprise. We are stronger by far than the sum of our individual parts. Our focus is in areas where our particular strengths add to or complement those of our partners throughout the national Regional Centers of Excellence (RCE) program. SERCEB is multidisciplinary team based in Region IV. The Prime Institution is the University of North Carolina Chapel Hill (UNC), and the other principal consortium members include Duke University, Emory University, Vanderbilt University, the University of Florida (Gainesville), and the University of Alabama at Birmingham. Our primary goal is to assist the nation in developing and deploying effective and rapid responses to biodefense and emerging infectious diseases threats. To this end, we will discover new therapies and principles by which effective new vaccines can be developed. Our pathways to discovery include better understanding of the pathogenic mechanisms by which pathogens cause disease and the nature of the immune responses against them. Hence, mechanistic studies on pathogenesis and animal models will also be a focus of study. We will concentrate on areas that offer promise for discovery of broad targets for therapy or prevention. We emphasize pathogen interactions with the innate immune system, an area of great SERCEB strength that offers excellent opportunities for discovery of broadly effective therapies. Discovery of new therapies also includes a focused screening and drug development team effort, which although not directly derived from studies of basic pathogenesis, depends in part on studies of pathogenesis to validate targets. Vaccine discovery is based on identification of crucial shared protective epitopes and protective, as opposed to deleterious, immune responses.